7,8-Benzoflavone, a synthetic substance, has been shown by Diamond and Gelboin to protect cultured rodent cells against DMBA-induced cytotoxicity, presumably by inhibiting mixed-function oxidase activity. Previously we found that 7,8-benzoflavone protects cultured rat liver epithelial-like cells against aflatoxin B1-induced cytotoxicity, suggesting that this carcinogen is activated by the same or similar mixed-function oxidase which activates DMBA. We now have evidence that 4 naturally occurring flavones, nobiletin, tangeretin, fisetin, and quercetin, also protect rat liver epithelial-like cells against aflatoxin B1-induced cytotoxicity and inhibit the binding of 3H-aflatoxin B1 to the DNA of the cells. These 4 flavones are natural constituents of edible foods and protect cultured cells against a mycotoxin that is a likely cause of human cancer. This raises the possibility that dietary flavones might affect the response of humans to aflatoxin carcinogens. In order to determine if the above flavones competitively inhibit the activation of aflatoxin B1, we are establishing an essay for the mixed-function oxidase using aflatoxin B1 as a substrate in which the rate of irreversible binding of aflatoxin B1 to macromolecules is measured.